Importance of Accurate Testing

HER2 Testing

Because of Herceptin's (trastuzumab) significant clinical benefits in extending survival for HER2+ metastatic breast cancer patients, it is important to accurately determine the HER2 status of all patients with invasive breast cancer.

How Can I Help To Ensure An Accurate HER2 Test Result?

IHC detects HER2 overexpression at the protein level, and may be affected by conditions of the testing procedures. These include: time to fixation, duration of fixation, processing, denaturation, heating, antigen retrieval, the staining procedure used, and the interpretation of staining.3,7 Although there are antigen retrieval techniques in use, these may result in false-positive IHC results. FISH measures HER2 DNA. Some fixatives, chemicals or heat, may interfere with the FISH assay. However, an internal control is used to distinguish between a FISH-negative and a non-informative result.6 Scoring difficulties associated with FISH testing may be caused by difficulties in identifying specific invasive cells to include in the determination.

HER2 testing should be performed by laboratories with demonstrated proficiency in the specific technology being utilized. Improper assay performance may result from the use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation and can lead to unreliable results. 1,8

Recent findings suggest the need to improve quality control measures in laboratories that use IHC assays, including periodic testing for concordance with FISH. These studies also suggest that large-volume reference laboratories performing HER2 tests are more reliable than small-volume laboratories.3,9 HER2 testing should be done in laboratories accredited to perform such testing. Ongoing proficiency testing is a necessary component of a laboratory's qualification for accreditation.

HER2 test results not always accurate 2

Rate of discordance* between initial test from local lab and subsequent central lab test was assessed in Herceptin adjuvant trial NSABP B-31

Graph: Discordance rates by type of test performed at local lab

*Discordance defined as differing HER2 test result between initial local testing and follow-up central testing as part of quality assurance protocol. Central lab tested IHC by HercepTest and FISH by PathVysion.

  • Certain testing considerations make it inadvisable to rely on a single method to rule out potential Herceptin benefit 1
  • Limitations in assay precision (particularly for the IHC method)
  • Limitations in the direct linkage between assay result and overexpression of the Herceptin target (for the FISH method)

Concordance with central lab correlated with greater testing experience 3

Rates of discordance were lower for labs with greater experience performing the test*

Graph: Discordance rates by lab experience

*Discordance defined as differing HER2 test result between initial local testing and follow-up central testing as part of quality assurance protocol. Central lab tested IHC by HercepTest and FISH by PathVysion.

Labs are required to demonstrate proficiency in specific assays to maintain CAP accreditation 4,5

Collaboration is key among specialists

Collaboration among specialists-including pathologists, surgeons, radiologists, and oncologists-is critical to help ensure accurate interpretation of results and appropriate disease management

Boxed WARNINGS and Additional Important Safety Information

  • Cardiotoxicity and Cardiac Monitoring
  • Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure (CHF) and decreased left ventricular ejection fraction (LVEF).
    • The incidence and severity of left ventricular cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens.
    • Discontinue Herceptin treatment in patients receiving adjuvant therapy and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function.
  • Patients should undergo monitoring for decreased left ventricular function before Herceptin treatment, and frequently during and after Herceptin treatment.
    • More frequent monitoring should be employed if Herceptin is withheld in patients who develop significant left ventricular cardiac dysfunction.
  • In one adjuvant clinical trial, cardiac ischemia or infarction occurred in the Herceptin-containing regimens.
  • Infusion Reactions, Pulmonary Toxicity and Neutropenia
  • Serious infusion reactions and pulmonary toxicity have occurred; fatal infusion reactions have been reported.
    • In most cases, symptoms occurred during or within 24 hours of administration of Herceptin. Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension.
    • Patients should be monitored until signs and symptoms completely resolve.
    • Discontinue Herceptin for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
  • Exacerbation of chemotherapy-induced neutropenia has also occurred.

Pregnancy Category D

Herceptin can cause oligohydramnios and fetal harm when administered to a pregnant woman.

Most Common Adverse Events

The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.

Please see the Herceptin full prescribing information including Boxed WARNINGS and additional important safety information.

  • References:
  • 1. Herceptin® (trastuzumab) Full Prescribing Information, Genentech, Inc. May 2008.
  • 2. Data on file. Genentech, Inc.
  • 3. Paik S, Bryant J, Tan-Chiu E, et al. Real-world performance of HER2 testing-National Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst.2002;94:852-854.
  • 4. Wolff AC, Hammond EH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. JClin Oncol.2007; 25: 118-145.
  • 5. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med.2007;131:18-43.
  • 6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Breast Cancer. 2008; 2:12,14, 30. Available at: http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Accessed November 3, 2008.
  • 7. O'Leary TJ. Standardization of immunohistochemistry. Appl Immunohistochem Mol Morphol. 2001; 9:3-8
  • 8. Roche PC, Suman VJ, Jenkins RB, et al. Concordance
  • 9. Roche PC, Suman VJ, Jenkins RB, et al. Concordance between local and central laboratory HER2 testing in the Breast Intergroup Trial N9831. J Natl Cancer Inst. 2002; 94:855-857.


Herceptin® (trastuzumab)Herceptin® (trastuzumab)

close

Share this page

Email this page